On January 31, 2022 Tollys, a biopharmaceutical company developing the first anti-cancer immunotherapy based on a synthetic Toll-Like Receptor 3 (TLR3) specific agonist, reported that it has renewed and extended its research collaboration started in 2020 with a global pharmaceutical company, a leader in immuno-oncology (Press release, Tollys, JAN 31, 2022, View Source [SID1234607500]). The company also announces the acceleration and expansion of its R&D platform in the fields of TLR3 agonist candidates for intravenous administration and Antibody-Drug-Conjugates (ADC, or AOC for Antibody-Oligonucleotide-Conjugates).

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Based on the strong preclinical data collected to date with locally administered TL-532, Tollys is also accelerating and expanding its internal and collaborative R&D activities on TLR3 agonist candidates designed for intravenous administration and antibody-drug-conjugates. Tollys is thus running several parallel preclinical programs using different vectorization and targeting methods for its TLR3 agonist candidate(s). According to Tollys, TL-532 is the first chemically conjugable specific TLR3 agonist usable as a payload with antibodies and other carriers.

This acceleration in the development of candidates for intravenous administration is in line with the recommendations of the international board of the European oncology innovation acceleration program MATWIN which awarded Tollys TLR3 agonist the status of ‘best-in-class innovation of the year’ in May 2021.

"Our renewed and extended pharma collaboration is further confirmation of the potential of specific TLR3 agonists. We are also very excited to advance our R&D programs for the selection of candidates for intravenous administration; we estimate that a lot more patients could benefit from treatment with TLR3 agonists, if administered intravenously rather than locally," said Vincent Charlon, CEO of Tollys.

About TL-532
TL-532 is the first synthetic specific TLR3 agonist with a proprietary defined double-stranded RNA sequence. As such, TL-532 has the potential to be the best-in-class and first-to-market TLR3 agonist. TL-532 was shown to have a triple mechanism of action inducing 1) death by apoptosis selective to cancer cells-not in normal cells, leading to the in-situ release of tumor specific antigens, 2) activation of the myeloid dendritic cells of the immune system to mount a specific T-cell response against the tumor antigens and 3) switch of the tumor microenvironment, by producing cytokines and chemokines which prevent tumor development. The result is the immunogenic cell death of tumor cells, together with an autovaccination preventing the recurrence of cancer.

On January 31, 2022 Immune-Onc Therapeutics, Inc. ("Immune-Onc"), a clinical-stage cancer immunotherapy company developing novel biotherapeutics targeting immunosuppressive myeloid checkpoints, reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for IO-202, a first-in-class antibody targeting leukocyte immunoglobulin-like receptor B4 (LILRB4, also known as ILT3), for the treatment of solid tumors (Press release, Immune-Onc Therapeutics, JAN 31, 2022, View Source [SID1234607529]).

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Myeloid cells are abundant and often immune suppressive in the solid tumor microenvironment. The LILRB4 receptor is expressed on monocytic myeloid cells, including dendritic cells, and contributes to a tolerogenic myeloid cell phenotype, resulting in decreased tumor immune surveillance. In preclinical data presented at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, IO-202 was found to enhance dendritic cell function and T cell activation in vitro and promote anti-tumor immunity in a solid tumor model in vivo. These data provided a strong rationale to evaluate the therapeutic potential of IO-202 as a myeloid checkpoint inhibitor in solid tumors.

"The FDA clearance to begin our Phase 1 study for IO-202 in solid tumors is a major milestone for Immune-Onc, which represents the third IND for our pipeline and the second for IO-202," said Charlene Liao, Ph.D., chief executive officer of Immune-Onc. "We know that high LILRB4 expression on myeloid cells infiltrating solid tumors contributes to tumor immune evasion. IO-202 is a first-in-class myeloid checkpoint inhibitor targeting LILRB4, which may provide therapeutic benefit to multiple solid tumor types where evasion of the immune system allows disease to progress and create resistance to therapy, including to T cell checkpoint inhibitors. We look forward to advancing IO-202 into the clinic to evaluate its potential as a monotherapy and in combination with an anti-PD-1 in patients with solid tumors."

The Phase 1, multicenter, dose-escalation and dose expansion study will consist of a monotherapy cohort and a combination therapy cohort to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of IO-202 alone and in combination with pembrolizumab, an anti-PD-1 antibody, followed by indication-specific expansion cohorts to be treated with IO-202 in combination with pembrolizumab at the recommended Phase 2 dose. Various biomarkers will be assessed to enable a mechanistic understanding of clinical data and inform future trials. This study may also provide an opportunity to identify preliminary efficacy signals.

ABOUT LILRB4 (also known as ILT3)

LILRB4, also known as ILT3, is an immune inhibitory transmembrane protein found on monocytic myeloid cells, including dendritic cells. LILRB4 inhibits antigen-presenting cell activation, resulting in immune tolerance. LILRB4 is also expressed on certain hematologic cancer cells and monocytic myeloid cells in the solid tumor microenvironment. Immune-Onc and The University of Texas published pioneering research in Nature illuminating the role of LILRB4 in immune suppression and tumor infiltration in acute myeloid leukemia (AML) and presented the rationale for targeting LILRB4 in solid tumors at the AACR (Free AACR Whitepaper) Annual Meeting 2021.

ABOUT IO-202

IO-202 is a first-in-class LILRB4 antagonist antibody with broad potential as an immunotherapy in both blood cancers and solid tumors. In hematologic malignancies, preclinical studies showed that IO-202 converts a "don’t kill me" to a "kill me" signal by activating T cell killing and converts a "don’t find me" to a "find me" signal by inhibiting infiltration of blood cancer cells. In solid tumors, preclinical data showed that IO-202 enhances dendritic cell function and T cell activation in vitro and inhibits tumor growth in a solid tumor model in vivo.

IO-202 is currently in Phase 1 clinical development for the treatment of AML and chronic myelomonocytic leukemia (CMML). The U.S. Food and Drug Administration granted IO-202 Orphan Drug Designations for treatment of AML in 2020. The company has received IND clearance to evaluate IO-202 in solid tumors in January 2022.

On January 31, 2022 Semmelweis University and AstraZeneca it’s Hungarian subsidiary reported that they have signed a strategic cooperation agreement to further investigate the links between certain common diseases, such as diabetes, chronic kidney disease (CKD) and heart failure, to strengthen and expand joint research and development activities, and to implement joint programmes to help treat, educate and diagnose patients (Press release, Semmelweis University, JAN 31, 2022, View Source [SID1234607513]). A framework agreement for clinical trials was also signed at the event, which will allow for faster and more efficient trial start-ups.

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„Today, an agreement is being signed between AstraZeneca, one of the world’s leading biotechnology pharmaceutical companies, which also has a dominant market position in Hungary, and Semmelweis University, the leading medical and health sciences higher education institution of the Central European region. What we certainly have in common is a commitment to research and development and a dedication to providing patients with better and more innovative therapies," highlighted Dr. Béla Merkely, rector of Semmelweis University on signing the strategic partnership cooperation agreement. „This cooperation will allow us to increase our joint research and development activities in the fields of oncology, cardiology, diabetology, nephrology and other areas of internal medicine. As a first step, a complex program on chronic kidney disease (CKD) could be implemented in collaboration with our Department of Family Medicine," the rector explained, adding that CKD is an under-diagnosed condition which can increase the risk of cardiovascular damage many times over.

Semmelweis University and AstraZeneca also signed a framework agreement for clinical trials. „This will enable the contracting of individual clinical trials, and thus the launching of trials and the involvement of patients, to be faster and more efficient. Currently, Semmelweis University takes part in two-thirds of AstraZeneca’s Hungarian trials, but our aim is to increase this to over 80 percent," Dr. Béla Merkely emphasized. The rector also pointed out that one of the university’s strategic objectives is to increase clinical research activity by building strategic partnerships with the pharmaceutical industry. This allows patients to have access to the most innovative therapeutic options as soon as possible, and increases scientific performance as well, which contributes to moving up the rankings.

Kuuno Vaher, AstraZeneca’s Cluster Country Director of Central Europe reminded that the company’s main therapeutic areas are oncology, cardiovascular diseases, renal and metabolic diseases, respiratory diseases and immunology. "We know a lot more about these diseases by now, but the implementation of these new information is becoming more challenging – more and more aspects need to be taken into account in treatment," Kuuno Vaher said. „This is why an important part of the company’s partnerships in different countries, including now Hungary, is to look at how to improve the organisation of healthcare and how to use digitalisation, to enable doctors making better healthcare decisions based on all the available data. Basically, there are four pillars of collaboration: diagnostics, screening, education and analyzing the accumulated data, to see if what we are doing is really improving patients’ lives. For example, it is not enough to know how many people are utilizing a certain medicine; we also need to see if an innovation is having a real impact on patients’ outcome," Kuuno Vaher pointed out.

Dr. Mátyás Faluvégi, Managing Director of AstraZeneca’s Research Division, explained that the framework agreement on clinical trials is based on the fact that Semmelweis University has an optimal background for conducting such trials. In the last three years, a total of 855 clinical trials have been conducted in Hungary, out of which AstraZeneca owned 49 projects, and the university was involved in 31. „A large number of cardiovascular and pulmonary trials are already taking place at Semmelweis, so our aim is to launch more oncology trials in the coming years," the managing director said. „By signing the agreement, we would like to accelerate the start-up of trials in the short term, and our long-term goal is to strengthen AstraZeneca’s presence not only at the university, but throughout Hungary," he added.

Dr. Péter Ferdinandy, Vice-Rector for Science and Innovation of Semmelweis University, thanked the Clinical Research Coordination Center led by Dr. János Filakovszky for the work done in the preparation of the agreement. He then expressed hope that the cooperation will further increase the number of clinical trials, which could be a first step towards the joint development of new therapies, as well as the creation of shared intellectual property and a broader boost to scientific cooperation.

The strategic cooperation agreement and the framework agreement on clinical trials were signed by Rector Béla Merkely and Chancellor Lívia Pavlik on behalf of Semmelweis University, while the former document was signed by Cluster Director Kuuno Vaher on behalf of AstraZeneca and the latter by Managing Director Mátyás Faluvégi.

On January 31, 2022 Children’s Hospital of Philadelphia (CHOP) reported that Fusion oncogenes, such as RET- and NTRK-gene fusions, are associated with more invasive pediatric thyroid cancers, correlating with the highest risk of metastases and a lower likelihood of achieving remission one year after initial therapy (Press release, CHOP, JAN 31, 2022, View Source [SID1234607530]). The findings, which were published in the Journal of Clinical Oncology, contrast those previously established in adults, for whom BRAF mutations, not fusion oncogenes, are associated with more invasive disease that is less response to therapy.

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"This study shows fusion oncogenes are more prevalent in pediatric thyroid cancer that is likely to spread to the lungs, whereas tumors with RAS-like and BRAF mutations are associated with low- and intermediate risk, respectively," said Andrew J. Bauer, MD, Director of the Pediatric Thyroid Center at Children’s Hospital of Philadelphia and senior author of the study. "This provides an opportunity for increased collaboration among surgeons, endocrinologists, and oncologists to stratify the treatment of tumors, approaching RAS-like mutations with less extensive surgery, while also exploring the new treatment protocols using FDA-approved oncogene specific inhibitors to optimize the treatment of patients with lung metastasis."

The results from the CHOP thyroid team are a pediatric-specific follow-on study to the 2014 Cancer Genome Atlas (TCGA) report that classified adult papillary thyroid cancer (PTC) into two molecular subtypes – RAS-like or BRAF-like – and concluded that molecular classification more accurately reflected tumor behavior, including disease severity and prognosis. To determine whether the adult based TCGA classification predicted the similar clinical behavior and outcomes in pediatric patients with DTC, the CHOP researchers analyzed 131 pediatric thyroid tumors. Of those, 66 were collected and sequenced using the CHOP Division of Genomic Diagnostics platform between 2016 and 2019, with the remaining 65 collected between 1989 and 2012 and sequenced on a commercial platform. In analyzing the sequenced samples, the researchers categorized mutated genes into three categories: RAS-mutant, BRAF-mutant, and RET/NTRK fusions. The researchers evaluated these categories against numerous parameters, including patient demographics, thyroid pathology, and clinical characteristics.

The researchers found that the three-tier classification system more accurately reflected the clinical behavior of DTC in pediatrics. Based on the low prevalence of RAS-mutant tumors among the pediatric samples and their low-risk of metastasis, the CHOP researchers limited their statistical analysis to comparing samples with a BRAF mutation to samples with RET/NTRK fusions. The researchers found no distant metastasis in any patients with BRAF-mutant thyroid tumors, whereas 36% of patients with RET/NTRK fusions had distant metastasis. Persistent disease at one year was also more frequent in the subgroup harboring RET/NTRK fusions: 36% vs. 17% among those with a BRAF mutation.

In line with prior studies, the researchers also found that RET/NTRK fusions are more common in PTC patients under the age of 10. Of the samples in their analysis, 91% of those in patients under the age of 10 harbored fusion events. The prevalence gradually decreased in pediatric patients older than 10 years (27%) and into adulthood (9%). By contrast, only one BRAF mutation (9%) was found among patients under the age of 10, compared with 25 pediatric patients aged 10 years or older (20%) and 58% of adults with PTC.

"Considering the high prevalence of RET/NTRK fusions in pediatric differentiated thyroid cancer, and their association with more metastatic behavior, it will be crucial to generate the transcriptional signatures of RET/NTRK and BRAF-mutant subgroups in the pediatric population to understand the differential impact of these alterations on signaling pathways, differentiation, and clinical outcomes," said first author Aime T. Franco, PhD, investigator in the Center for Childhood Cancer Research and director of the Pediatric Thyroid Cancer Translational Research Laboratory at Children’s Hospital of Philadelphia. "Future research in our Thyroid Center Frontier Program at CHOP will also investigate the underlying reason for the significant differences between children and adults when it comes to invasive disease, as well as the role of BRAF and RET/NTRK in response to radioiodine therapy."

Franco AT, Ricarte-Filho JC, Isaza A, Jones Z, Jain N, Mostoufi-Moab S, Surrey L, Laetsch TW, Li MM, DeHart JC, Reichenberger E, Taylor D, Kazahaya K, Adzick NS, and Bauer AJ. "Fusion Oncogenes Are Associated with Increased Metastatic Capacity and Persistent Disease in Pediatric Thyroid Cancers," Journal of Clinical Oncology, online January 11, 2022, DOI: 10.1200/JCO.21.01861

On January 31, 2022 Aethlon Medical, Inc. (Nasdaq: AEMD), a company developing medical technology to treat cancer and life-threatening infectious disease, reported that it will issue financial results for its third quarter fiscal year 2022, ended December 31, 2021, at 4:15 p.m. EST on Monday, February 14, 2022 (Press release, Aethlon Medical, JAN 31, 2022, https://www.prnewswire.com/news-releases/aethlon-medical-to-release-third-quarter-financial-results-and-host-conference-call-on-february-14-2022-301471097.html [SID1234607531]).

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Management will host a conference call on Monday, February 14, 2022 at 4:30 p.m. EST to review financial results and recent corporate developments. Following management’s formal remarks, there will be a question and answer session.

Interested parties can register for the conference by navigating to View Source Please note that registered participants will receive their dial in number upon registration.

Interested parties without internet access or unable to pre-register may dial in by calling:

All callers should ask for the Aethlon Medical, Inc. conference call.

A replay of the call will be available approximately one hour after the end of the call through March 14, 2022. The replay can be accessed via Aethlon Medical’s website or by dialing 1-877-344-7529 (domestic) or 1-412-317-0088 (international) or Canada toll free at 1-855-669-9658. The replay conference ID number is 2728183.